3 years ago

Metformin-induced reduction of CD39 and CD73 blocks myeloid-derived suppressor cell activity in patients with ovarian cancer.

Jingli Lu, Xinfeng Chen, Tengfei Zhang, Zhen Zhang, Jianmin Huang, Guohui Qin, Jie Zhao, Jane Yu, Xuan Zhao, Lan Huang, Bin Zhang, Jieyao Li, Yi Zhang, Dan Wang, Wenhua Xue, Lifeng Li, Qianyi He, Yu Ping, Feng Li, Zhi Sun, Hong Li, Dongli Yue, Li Yang, Zhirui Fan, Liping Wang, Qun Gao, Chaoqi Zhang
Metformin is a broadlyprescribed drug for type 2 diabetes that exerts antitumor activity, yet the mechanisms underlying this activity remain unclear. We show here that metformin treatment blocks the suppressive function of myeloid-derived suppressor cells (MDSC) in patients with ovarian cancer (OC) by downregulating the expression and ectoenzymatic activity of CD39 and CD73 on monocytic and polymononuclear MDSC subsets. Metformin triggered activation of AMP-activated protein kinase α (AMPKα) and subsequently suppressed hypoxia-inducible factor-α (HIF-1α), which was critical for induction of CD39/CD73 expression in MDSC. Furthermore, metformin treatment correlated with longer overall survival in diabetic patients with OC, which was accompanied by a metformin-induced reduction in the frequency of circulating CD39+CD73+MDSC and a concomitant increase in the antitumor activities of circulating CD8+T cells. Our results highlight a direct effect of metformin on MDSC and suggest that metformin may yield clinical benefit through improvement of antitumor T cell immunity by dampening CD39/CD73-dependent MDSC immunosuppression in OC patients.

Publisher URL: http://doi.org/10.1158/0008-5472.CAN-17-2460

DOI: 10.1158/0008-5472.CAN-17-2460

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.